Objectives: 1) Preliminary studies indicate that density dependent inhibition of proliferation is differentially restored to transformed cells by increasing the proportion of solid phase lipid in membranes. This phenomenon will be further characterized to study kinetic responses of cellular macromolecular synthesis to shifts in growth temperature which restore or result in the loss of density dependent inhibition of proliferation. 2) The effects of membrane physical state on regulation of synthesis of the key enzyme in cholesterol biosynthesis will be determined. 3) Polymethacrylate beads, underivatized or derivatized with lectins, will be used to patch and capture lectin receptors from untransformed and oncogenically transformed fibroblasts. Phagosomes will be isolated, and the enrichment of proteins (labeled prior to phagocytosis by lactoperoxidase catalyzed iodination or other means) in the phagosomes will be determined to test for pleitropy indicative of cytoskeletal attachment. 4) A study of the molecular determinants of cell shape and surface architecture will utilize human erythrocytes from normal subjects and those who suffer from hereditary disorders such as spherocytosis, elipsocytosis, myotonic and Duchenne dystrophies. Similar studies will be initiated with newly established epidermal lines from dystrophic, carrier (Duchenne) and normal subjects. Organization of proteins within the membranes will be determined using dissociable cross linking agents to demonstrate interactions between membrane protein species. Effects of stressing agents (cold, colchicine, etc.) will be assessed both by analysis of alterations in cross linking of proteins, and by analysis of cell shape by scanning emission microscopy. Demonstration of differences between cells from normal, carrier and affected subjects could lead to development of techniques for prenatal diagnosis.